Studies were made to isolate and characterize "transforming genes" incorporated into the genome of non-transforming type-C viruses and to employ these new viruses to develop immunological reagents against the products of their transforming genes. New variant murine type-C viruses were isolated and used to define mechanisms for potentiation or attenuation of viral strains. Findings included (a) differences in infectivity between low and high leukemia viruses were directly related to leukemogenicity, (b) the major biochemical difference was within the envelope-gene region and affected the antigenicity of the major viral envelope glycoprotein, (c) leukemogenicity of nondefective viruses seems to be a function of replication efficiency, (d) the susceptibility of cells to infection determined the target tissue for transformation by rapid replicating viruses, (e) the chromosome residence was identified for the receptor-gene code for various classes of viruses, including the new isolates, (f) transplanted tumor cells induced by certain viruses did not grow at the site of inoculation but "homed" into the specific tissue in which it arose originally showing a dependence on that hormonal or tissue factor microenvironment.